Parkinsons disease

Presented by: Meera Qaiser

What is parkinsons disease• Parkinson's disease is the second most common

neurodegenerative disorder and the most common movement disorder.

• The progression of Parkinson's disease and the degree of impairment vary from individual to individual.

• In the United States, about 1 million people are affected by Parkinson's disease and worldwide about 5 million.

• Most individuals who develop Parkinson's disease are 60 years of age or older.

• Descriptions of Parkinson's disease date back as far as 5000 BC.

• Parkinson's disease was named after the British doctor James Parkinson, who in 1817 first described the disorder in great detail as "shaking palsy."

Primary symptoms

• Tremors: Trembling in fingers, hands, arms, feet, legs, jaw, or head.

• Rigidity: Stiffness of the limbs and trunk, which may increase during movement.

• Bradykinesia: Slowness of voluntary movement.

• Postural instability: Impaired or lost reflexes can make it difficult to adjust posture to maintain balance. Postural instability may lead to falls.

• Parkinsonian gait: Individuals with more progressive Parkinson's disease develop a distinctive shuffling walk with a stooped position and a diminished or absent arm swing.

Secondary symptoms

• anxiety, insecurity, and stress• confusion, memory loss, and dementia (more common in

elderly individuals)• constipation• depression• difficulty swallowing and excessive salivation• diminished sense of smell• increased sweating• male erectile dysfunction• skin problems• slowed, quieter speech, and monotone voice• urinary frequency/urgency

S-nitrosylation of parkin

• mutations in the parkin gene are known to cause parkinsondisease.

• The parkin gene encodes an ubiquitin E3 ligase that targets many proteins for proteasomal degradation and also has a neuroprotective role in PD-related apoptotic events

• Mutations in the parkin gene result in the disturbances in parkin-mediated protein ubiquitination ,which leads to the accumulation of potentially neurotoxic protein aggregates of parkin substrates with consequent dysfunction of the ubiquitin-proteasome system degradative pathway.

• Interestingly, recent reports suggest that, independently from its ubiquitin-ligase role, parkin also functions as a transcriptional repressor of p53 to protect dopaminergicneurons from PD-related stress.

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• In addition to these rare mutations, several environmental toxins that trigger oxidative/nitrosative stress are believed to affect the enzymatic activity of parkin protein.

• Parkin has multiple cysteine residues in its RING domain and elsewhere , which can react with NO to form SNO-parkin.

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• This S-nitrosylation reaction compromises parkin’s neuroprotectivefunction. Our group reported that S-nitrosylation of parkin initially increases E3 ligase activity, but with additional time this activity is inhibited. This dysfunctional E3 ligase activity is associated with abnormal protein aggregation resembling Lewy bodies, thus contributing to the parkinsonian phenotype

• Moreover, S-nitrosylation of parkin has also been found in brains of human patients with Lewy body disease (LBD) and PD .

• These findings support our notion that posttranslational changes to PD-related proteins via S-nitrosylation or other oxidation reactions may well contribute to the PD.

treatment• There is currently no treatment to cure Parkinson's disease. Several

therapies are available to delay the onset of motor symptoms.

• The most effective therapy for Parkinson's disease is levodopa(Sinemet), which is converted to dopamine in the brain.

• However, because long-term treatment with levodopa can lead to unpleasant side effects (a shortened response to each dose, painful cramps, and involuntary movements), its use is often delayed until motor impairment is more severe.

• In earlier stages of Parkinson's disease, substances that mimic the action of dopamine (dopamine agonists), and substances that reduce the breakdown of dopamine (monoamine oxidase type B (MAO-B) inhibitors) can be very efficacious in relieving motor symptoms.